The present invention is directed to an improved method of delivering pharmaco-therapeutic agents in which the time required for drug delivery into a patient's blood stream is substantially reduced. The delivery is direct to the blood stream, but non-invasive, non-disruptive, and pain-free. Examples of the classes of pharmaco-therapeutic agents which may be delivered in accordance with the present invention include such as: opioid-receptor agonists/antagonists, dopamine-receptor agonists/antagonists, serotonin-receptor agonists/antagonists, monoamine transporter agonists, antimanic agents, anti-smoking agents and immunogenic therapies (antibody products to reduce peripheral levels of drug substances), vaccines, antibiotics, high blood pressure drugs, heart medications, asthma medications, sexual dysfunction medications, analgesics, anesthesia drugs, insulin, and the like.
There are four general types of drug delivery currently available: oral, injection either intravenous, subcutaneous or transdermal, implants, and inhalation. Each of the methods has advantages and disadvantages.
1. Oral administration is acceptable in most cases except that the drug delivery rate is often too slow and it can cause digestive tract upset.
2. Intravenous injection is effective, but is intrusive, painful, has a danger of causing adverse reactions from the body due to a high concentration drug flowing through one small pathway, and presents a danger of infection both for the patient and the health-giver alike. Also if the injections have to occur frequently, such as once or twice a day for insulin as an example, there is a problem of running out of injectable locations let alone pain, bruises and danger of infections. Transdermal injection can be an answer to a lot of problems but has not been widely used. The technology is still in early stages of development.
3. Implants are used to avoid multiple shots and to maintain constant dosage over a long period of time, but requires invasive surgery.
4. Inhalation is an ideal drug delivery method. It can be done widely and conveniently because it is very fast and non-intrusive. Inhalants such as for asthma have shown a lot of promise but they are still not completely satisfactory. They take effect very rapidly, sometimes even faster than intravenous injection, but the inhalant method is currently limited to a few medications due to the difficulties of forming suitable dispersions for delivery into the lungs. Also most inhalants today use a chlorofluoro compound (CFC) as a dispersant and there is a movement to move away from CFC's for environmental reasons as well as suspected harmful effects that CFC's might have inside the body.
The development of the first pressurized metered dose inhaler (MDI) in the mid-1950s was a major advance in the administration of drugs locally to the lung, especially for the treatment of asthmatics. More recently, research has focused on using the lung as a conduit to deliver biomolecules such as peptides and proteins to the systemic circulation. Sophisticated dry powder inhaler (DPI) and metered solution devices have also been designed, both to improve deep-lung delivery and to address the MDI actuation/breath coordination issue that is problematic for certain patients. Relatively little development effort has been applied to improve pulmonary drug delivery by means of new formulation strategies.
One attempt to produce an improved inhalant drug delivery system is that of Alliance Pharmaceutical which is based upon “PulmoSpheres” which are prepared by mixing a drug and a surfactant to form an emulsion and then spray-drying the emulsion to cause the drug to be encased in the shells of hollow, porous, microscopic surfactant spheres. The resultant powder is then suspended in a fluorochemical or other propellant or carrier for delivery of the drug medications into the lungs or nasal passages of a patient. The hollow/porous morphology of the microspheres allows non-aqueous liquid propellants such as fluorochemicals to permeate within the particles, improving suspension stability and flow aerodynamics while impeding particle aggregation. U.S. Pat. No. 6,123,936 utilizes this technology to produce a dry powder formulation for interferons. Use of the spray-drying process precludes the preparation of products from any heat-sensitive pharmaceuticals since the drying must be conducted at elevated temperature, i.e. about 50 to 200° C. (122–392° F.)
Moreover, the densities of porous particles that can be produced by a spray-drying process, although much lower than many currently available solid or liquid inhalant particles, are still too high for many uses resulting in too much of the drug which is being delivered not reaching the lung surfaces.
The porosity and surface area of the aerogel products of this invention are much higher than those of spray-dried particles. The density of the aerogel products, which can be as low as about 0.003 g/cc, is much lower than both the PulmoSpheres (about 0.1 g/cc) and that of crystalline powders (about 1 g/cc). As a result, the aerogel inhalants of this invention float much longer resulting in more pharmaceutical material reaching the inner part of lungs. Thus the delivery efficiency is improved.
Although the primary intended use of aerogels heretofore has been in the field of insulation, some inorganic oxide aerogels have been used as carriers for the delivery of agricultural, veterinary medicines, and pharmaceuticals. For example, Australian Patent 711,078 discloses the use of aerogels prepared from inorganic oxides like silica by surface modifying them for hydrophobicity and then use as carriers in agricultural and veterinary medicine, i.e. to carry an active material such as insecticides, nematicides, etc. as well as viruses, bacteria, and other microorganisms. Australian Patent 9965549 discloses the use of inorganic aerogels as carriers for pharmaceutically active compounds and preparations as solid, semisolid and/or liquid oral preparations.
None of the prior aerogels and uses thereof are related to aerogel particles which are soluble in pulmonary surfactant or the use of such particles as a dosage form for delivery of a pharmaceutical by inhalation as in the present invention.
It is an object of this invention to substantially increase the applicability of inhalation drug delivery to wider class of drugs by producing them in the form of aerogel powders.
It is a further object of this invention to formulate an aerogel powder form of a drug so that it is capable of reaching much of the available mucous area inside the lungs.
It is a further object of this invention to formulate an aerogel powder form of a drug for quick dissolution and introduction into the blood stream of mammals and quick release of the drug.
It is a further object of this invention to formulate an aerogel powder form of a drug for quick introduction into the blood stream of mammals and controlled release of the drug thereafter.
It is a further object of this invention to formulate an aerogel powder form of a drug for a long shelf life by making it physico-chemically stable in its composition and packaging.
It is a further object of this invention to produce devices and equipment suitable for delivery of an aerogel powder form a drug.
It is a further object of this invention to produce a controlled drug administration environment, e.g. room, in which drug delivery may be done passively, without coercion, man-handling, or intrusive measures.